Adoptive immunotherapy holds great potential as a therapeutic modality for the treatment of a variety of diseases including cancer and chronic viral infections. Central to these therapeutic approaches are controllable platforms for ex vivo activation of T cells. Several cell-based and artificial substrate systems have been described (June, 2007, J Clin Invest. 117(5): 1204-12).
Agonist antibodies to CD3 and CD28 immobilized on rigid materials, for example, polystyrene plastic and glass, have been utilized for the activation and expansion of T cells. However, T cells are unlikely to encounter a stimulatory surface with the stiffness of plastic in vivo, and the stiffness of the solid supports used for ex vivo culture of T cells may have important influences on their activation, proliferation, and differentiation that could impact their use in adoptive immunotherapy.
Current immunotherapy technologies reprogram T cells ex vivo to target leukemia. During this process, cells are transfected and expanded. One such method for facilitating T cell expansion involves Dynabeads™, for example, 4.5-um diameter polystyrene beads mixed with cells for high surface area-to-volume ratio. T cell signaling, proliferation, and expansion has been linked to the rigidity of the surface on which they are cultured—finding optimal expansion on “softer” surfaces (Young's Modulus or elastic modulus, “E,” of bulk materials less than 100 kPa as compared to a Young's Modulus, E, of greater than 2 MPa).
However, there is a need to develop further expansion platforms that allow for the fine-tuning of surface and/or matrix rigidity while maintaining a high area-to-volume ratio, which can be important to cell culture and practicality of clinical use. To this end, the electrospun mesh described herein offers an improved area-to-volume ratio and has many parameters that can be altered to tune rigidity and additional properties of interest, for example, polymer composition, fiber diameter, and mesh porosity.